Harnessing the 1,3-azadiene-anhydride reaction for the regioselective and stereocontrolled synthesis of lactam-fused bromotetrahydropyrans by bromoetherification of lactam-tethered trisubstituted tertiary alkenols.
| Autor: | Anosike IS; Department of Chemistry, Central Washington University Ellensburg WA 98926 USA Timothy.beng@cwu.edu., Beng TK; Department of Chemistry, Central Washington University Ellensburg WA 98926 USA Timothy.beng@cwu.edu. |
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| Jazyk: | angličtina |
| Zdroj: | RSC advances [RSC Adv] 2024 Jun 10; Vol. 14 (26), pp. 18501-18507. Date of Electronic Publication: 2024 Jun 10 (Print Publication: 2024). |
| DOI: | 10.1039/d4ra02523g |
| Abstrakt: | Halo-cycloetherification of lactam-tethered alkenols enables the construction of oxygen-heterocycles that are fused to nitrogen heterocycles via intramolecular halonium-induced nucleophilic addition. Specifically, tetrahydropyrans (THPs) that are fused to a nitrogen heterocycle constitute the core of several bioactive molecules, including tachykinin receptor antagonists and alpha-1 adrenergic antagonists. Although the literature is replete with successful examples of the halo-cycloetherification of simple mono- or disubstituted primary alkenols, methods for the modular, efficient, regioselective, and stereocontrolled intramolecular haloetherification of sterically encumbered trisubstituted tertiary alkenols are rare. Here, we describe a simple intramolecular bromoetherification strategy that meets these benchmarks and proceeds with exclusive 6- endo regioselectivity. The transformation employs mild and water-tolerant conditions, which bodes well for late-stage diversification. The hindered ethers contain four contiguous stereocenters as well as one halogen-bearing tetrasubstituted stereocenter. Competing Interests: There are no conflicts of interest to declare. (This journal is © The Royal Society of Chemistry.) |
| Databáze: | MEDLINE |
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